Information Encoded in the Sequence-Dependent Mechanics of DNA

项目1研究了一种新的遗传信息，它直接编码在基因组DNA序列中，通过DNA本身依赖于序列的机械特性。这些信息直接叠加在先前识别的蛋白质编码和调控信号之上，并基于DNA本身的序列相关机械特性。基因组可以利用这些信息通过限制详细的DNA序列来调整含有这种严重扭曲的DNA的蛋白质-DNA复合体的稳定性，即使这些DNA序列没有直接与任何蛋白质接触。遗传密码和许多DNA结合调节蛋白目标位点的简并，使得这种新的依赖于序列的机械信息可以叠加或多路传输在其他类型的遗传信息之上，而不会扭曲或交叉干扰。DNA以这种方式急剧扭曲的基本生物结构的例子包括真核细胞核小体(真核DNA的75%-90%被组织在其中)，以及许多含有双链DNA(dsDNA-)的病毒，以及许多细菌和真核蛋白质-DNA基因调控复合体。项目1结合了理论和实验方法，以发展对这些根本重要的DNA序列依赖机制的预测性机制的理解。

Project 1 investigates a novel kind of genetic information that is encoded directly in the genomic DNA sequence, through the sequence-dependent mechanical properties of DNA itself. This information is superimposed directly on top of protein coding and regulatory signals that were previously recognized, and is based on the sequence-dependent mechanical properties of the DNA itself. Genomes can use this information to tune the stability of protein-DNA complexes containing such sharply distorted DNA through constraints on the detailed DNA sequence, even when these DNA sequences are not contacted directly by any proteins. The degeneracy of the genetic code, and of many DNA binding regulatory proteins' target sites, allow this novel sequence-dependent mechanical information to be superimposed, or multiplexed on top of other kinds of genetic information without distortion or cross-interference. Examples of essential biological structures in which DNA is sharply distorted in this way include eukaryotic nucleosomes (in which 75-90% of all eukaryotic DNA is organized), and also many double-strand DNA- (dsDNA-) containing viruses, and many bacterial and eukaryotic protein-DNA gene regulatory complexes. Project 1 combines theoretical and experimental approaches to develop a predictive mechanistic understanding of these fundamentally important sequence-dependent mechanics of DNA.